Diabetes and hypertension: Pivotal involvement of purinergic signaling

Reichert, Karine Paula; Castro, Milagros Fanny Vera; Assmann, Charles Elias; Bottari, Nathieli B.; Miron, Vanessa Valéria; Cardoso, Andréia Machado; Stefanello, Naiara; Morsch, Vera Maria; Schetinger, Maria Rosa Chitolina

doi:10.1016/j.biopha.2021.111273

Cited by 31 publications

(30 citation statements)

References 260 publications

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“…A robust body of evidence supports the involvement of purinergic signaling in several disease conditions, such as cancer [ 17 , 22 – 28 ], inflammatory process [ 29 ], diabetes, and hypertension [ 30 , 31 ]. Recently, studies have hypothesized the potential role of purinergic signaling in COVID-19 [ 32 – 35 ].…”

Section: Introductionmentioning

confidence: 99%

High levels of extracellular ATP lead to different inflammatory responses in COVID-19 patients according to the severity

et al. 2022

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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has significantly impacted the world and has driven many researchers into the pathophysiology of COVID-19. In the findings, there is a close association between purinergic signaling and the immune response. Then, this study aimed to evaluate alterations in the purinergic signaling in COVID-19 patients according to range severity. We divided the COVID-19 patients into moderate and severe cases following the guideless of NIH and WHO, together with clinical characteristics. The blood samples were collected to obtain PBMCs and platelets. We analyzed the ectonucleotidase activities through ATP, ADP, AMP, Ado hydrolysis, E-NTPDase1 (CD39), and 5′-NT (CD73) expression by flow cytometry in total leukocytes. The extracellular ATP was measured by bioluminescence, and cytokines were analyzed by flow cytometry. We observed a decrease in ATP hydrolysis and increased AMP hydrolysis in PBMCs for both groups. In severe cases, ATP hydrolysis was raised for the platelets, while ADP and AMP hydrolysis have risen significantly in both groups. Additionally, there was a significant increase in ADP hydrolysis in severe cases compared to moderate cases. In addition, we observed an increase in the ADA activity in platelets of moderate patients. Moderate and severe cases showed increased expression of CD39 and CD73 in total leukocytes. To finalize the purinergic signaling, extracellular ATP was increased in both groups. Furthermore, there was an increase in IL-2, IL-6, IL-10, and IL-17 in moderate and severe groups. Thus, for the first time, our findings confirm the changes in purinergic signaling and immune response in COVID-19, in addition to making it more evident that the severity range directly impacts these changes. Therefore, the therapeutic potential of the purinergic system must be highlighted and studied as a possible target for the treatment of SARS-CoV-2 disease. Key messages COVID-19 patients exhibit alterations in purinergic system and immune response. High levels of extracellular ATP lead to different inflammatory responses. CD39 and CD73 expression were increased in COVID-19 patients. Cytokines IL-2, IL-6, IL-10, and IL-17 also were altered in these patients. The purinergic system may be a possibility target to SARS-CoV-2 treatments. Graphical abstract

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Section: Introductionmentioning

confidence: 99%

High levels of extracellular ATP lead to different inflammatory responses in COVID-19 patients according to the severity

et al. 2022

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“…As stated before Akt, a major component, plays a key role in the insulin-regulated GLUT4 trafficking. Decreased expression of Akt leads to decline in the expression of GLUT4 (Glucose transporter) in skeletal muscle of type-2 diabetic rats [ 26 ]. β-Caryophyllene treatment significantly enhanced the gene ( Figure 2B ) and protein ( Figure 3B ) expression of GLUT 4 as a result of increased Akt activation in skeletal muscle, which in turn significantly increased the glucose uptake, and oxidation in skeletal muscle of type-2 diabetic rats.…”

Section: Resultsmentioning

confidence: 99%

Effect of ß-Caryophyllene on insulin resistance in skeletal muscle of high fat diet and fructose-induced type-2 diabetic rats

Mani¹

2021

Bioinformation

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High fat diet feeding results in hyperglycemia and insulin resistance, which is a major pathological feature of type-2 diabetes mellitus. The use of oral hypoglycaemic drugs is limited due to its deleterious side effects and there is a need to find more efficacious agents for diabetes management. Hence, it is of interest to show the mechanism of action of ß-Caryophyllene on insulin signalling molecules in gastrocnemius muscle of high fat diet- induced type-2 diabetic rats. An oral effective dose of with ß-Caryophyllene (200 mg/kg b.wt) was given for 30 days to high fat diet (comprising 2% cholesterol, 1% cholic acid, 30% coconut oil, 67% conventional rat feed) and fructose fed type-2 diabetic rats to find out whether ß-Caryophyllene regulates IRS-1/Akt pathway of insulin signalling. The data shows that, ß-Caryophyllene treatment significantly increased the mRNA and protein expression of insulin receptor (IR) in diabetic rats whereas there is no significant difference in mRNA expression of insulin receptor-substrate-1 (IRS-1) was observed among groups. The Akt mRNAand GLUT-4mRNA and protein level were also improved in gastrocnemius muscle of type-2 diabetic rats. Thus, we concluded that ß–Caryophyllene could be used as potential phyto medicine for type-2 diabetes management.

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“…Purinergic signalling involves multiple receptors and extracellular enzymes that provides a system of cell-cell communication through the recognition and degradation of extracellular nucleotides and adenosine. An increasing number of studies have placed the purinergic system as a key player in numerous physiopathological conditions, including those involved in the in ammatory response such as T2DM 34 . Moreover, our data show signi cant activation of renin-angiotensin signalling at 4 h post HG treatment, however not in NG conditions.…”

Section: Discussionmentioning

confidence: 99%

Hyperglycemic conditions induce rapid cell dysfunction-promoting transcriptional alterations in human aortic endothelial cells

Bayaraa

Inman

Thomas

et al. 2022

Preprint

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Hyperglycemia is a major risk factor in the development of diabetic complications and promotes vascular complications through dysregulation of endothelial cell function. Various mechanisms have been proposed for endothelial cell dysregulation but the early transcriptomic alterations of endothelial cells under hyperglycemic conditions are not well documented. Here we use deep time-series RNA-seq profiling of human aortic endothelial cells (HAECs) following exposure to normal (NG) and high glucose (HG) conditions over a time course from baseline to 24 hours to identify the early and transient transcriptomic changes, alteration of molecular networks, and their temporal dynamics. The analysis revealed that the most significant pathway activation/inhibition events take place in the 1- to 4-hour transition and identified distinct clusters of genes that underlie a cascade of coordinated transcriptional events unique to HG conditions. Temporal co-expression and causal network analysis implicate the activation of type 2 diabetes (T2D) and growth factor signalling pathways including STAT3 and NF-κB. These results document HAEC transcriptional changes induced by hyperglycemic conditions and provide basic insight into the rapid molecular alterations that promote endothelial cell dysfunction.

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Diabetes and hypertension: Pivotal involvement of purinergic signaling

Cited by 31 publications

References 260 publications

High levels of extracellular ATP lead to different inflammatory responses in COVID-19 patients according to the severity

High levels of extracellular ATP lead to different inflammatory responses in COVID-19 patients according to the severity

Effect of ß-Caryophyllene on insulin resistance in skeletal muscle of high fat diet and fructose-induced type-2 diabetic rats

Hyperglycemic conditions induce rapid cell dysfunction-promoting transcriptional alterations in human aortic endothelial cells

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